Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination
Nasal DNA-MVA SIV vaccination provides more significant protection from progression to AIDS than a similar intramuscular vaccination
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DOI：
10.1038/mi.2009.103
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发表时间：
2009-11-01
影响因子：
8
通讯作者：
Aldovini, A.
中科院分区：
文献类型：
--
作者：
Manrique, M.;Kozlowski, P. A.;Aldovini, A.
预防性人类免疫缺陷病毒 (HIV) 疫苗接种可能需要在粘膜部位诱导病毒特异性免疫反应，以在接触后局部抑制病毒感染，因为大多数 HIV 感染是通过粘膜表面发生的。我们比较了鼻内或肌内猿猴免疫缺陷病毒 (SIV)+ 白介素 (IL)-2+IL-15 DNA/SIV-MVA（改良痘苗病毒安卡拉）疫苗接种在直肠内攻击 SIVmac251 的恒河猴中预防疾病进展的功效。经鼻接种疫苗的动物的 SIV 特异性直肠 IgA 反应比肌肉注射疫苗的动物更持久。尽管鼻腔免疫在结直肠粘膜中诱导了更显着的抗 SIV T 细胞反应，但两组之间的全身 T 细胞反应程度没有观察到显着差异。攻击后，两个疫苗接种组均观察到 CD4(+) 中央记忆 (CM) T 细胞保存和显着的疾病延迟。然而，与肌肉注射疫苗组或对照组相比，经鼻疫苗接种的动物循环和结直肠CD4(+) C M T细胞、循环CD4(+)/α 4 β 7(+)效应记忆(E-M) T细胞的早期保存更显着，并且无病间隔更长。无论疫苗接种状态如何，在动物中检测到长期病毒血症控制和 CD4(+) C-M T 细胞保存，其全身性 CD8(+)/肿瘤坏死因子 (TNF)-α(+) 和 CD8(+)/干扰素 (IFN)-gamma(+) T 细胞反应显着较高，结直肠 T 细胞中 SIV 特异性 CD4(+)/IL-2(+) 反应也较高。
Preventive human immunodeficiency virus (HIV) vaccination may require induction of virus-specific immune responses at mucosal sites to contain viral infection locally after exposure, as most HIV infections occur through mucosal surfaces. We compared the efficacy of an intranasal or intramuscular Simian immunodeficiency virus (SIV)+ interleukin (IL)-2+IL-15 DNA/SIV-MVA (modified vaccinia virus Ankara) vaccination in preventing disease progression in SIVmac251 intrarectally challenged rhesus macaques. SIV-specific rectal IgA responses were more significantly persistent in nasally vaccinated than in intramuscularly vaccinated animals. No significant differences were observed in the magnitude of systemic T-cell responses between the two groups, although the nasal immunization induced more significant anti-SIV T-cell responses in the colorectal mucosa. After challenge, CD4(+) central memory (C M) T-cell preservation and significant disease-delay were observed in both vaccination groups. However, nasally vaccinated animals had more significant early preservation of circulating and colorectal CD4(+) C M T cells, of circulating CD4(+)/alpha 4 beta 7(+) effector memory (E-M) T cells, and a longer disease-free interval when compared with the intramuscularly vaccinated or control groups. Regardless of vaccination status, long-term viremia control and preservation of CD4(+) C-M T cells was detected in animals with significantly higher systemic CD8(+)/tumor necrosis factor (TNF)-alpha(+) and CD8(+)/interferon (IFN)-gamma(+) T-cell responses and higher SIV-specific CD4(+)/IL-2(+) responses in colorectal T cells.